Understanding the mechanical response of double-stranded DNA and RNA under constant stretching forces using all-atom molecular dynamics
Understanding the mechanical response of double-stranded DNA and RNA under constant stretching forces using all-atom molecular dynamics
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DOI：
10.1073/pnas.1705642114
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发表时间：
2017-07-03
影响因子：
11.1
通讯作者：
Moreno-Herrero, Fernando
中科院分区：
文献类型：
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作者：
Marin-Gonzalez, Alberto;Vilhena, J. G.;Moreno-Herrero, Fernando
多种生物过程涉及核酸 (NA) 的拉伸。拉伸力会引起分子结构的局部变化，抑制或促进蛋白质的结合，最终影响其功能。了解力如何在原子水平上引起 NA 结构的变化是一个挑战。在这里，我们使用全原子、微秒长的分子动力学来模拟 dsDNA 和 dsRNA 受到高达 20 pN 拉伸力的结构。我们确定了 dsDNA 和 dsRNA 的所有弹性常数，并对这两种分子的机械响应中的三个显着差异提供了解释：dsRNA 获得的三倍软拉伸常数、相反的扭转-拉伸耦合及其非平凡的力依赖性。较低的 dsRNA 拉伸阻力与其更开放的结构有关，而两个分子的相反扭转拉伸耦合是由于分子链间距离随拉伸力的不同演化而造成的。该距离的缩短会导致双链 DNA 过度缠绕。相比之下，dsRNA 无法减少其链间距离，只能通过解旋来延长。链间距离与滑动碱基对参数直接相关，并且其在 dsDNA 和 dsRNA 中的不同行为可追溯到这些 NA 糖褶角的变化。
Multiple biological processes involve the stretching of nucleic acids (NAs). Stretching forces induce local changes in the molecule structure, inhibiting or promoting the binding of proteins, which ultimately affects their functionality. Understanding how a force induces changes in the structure of NAs at the atomic level is a challenge. Here, we use all-atom, microsecond-long molecular dynamics to simulate the structure of dsDNA and dsRNA subjected to stretching forces up to 20 pN. We determine all of the elastic constants of dsDNA and dsRNA and provide an explanation for three striking differences in the mechanical response of these two molecules: the threefold softer stretching constant obtained for dsRNA, the opposite twist-stretch coupling, and its nontrivial force dependence. The lower dsRNA stretching resistance is linked to its more open structure, whereas the opposite twist-stretch coupling of both molecules is due to the very different evolution of molecules' interstrand distance with the stretching force. A reduction of this distance leads to overwinding in dsDNA. In contrast, dsRNA is not able to reduce its interstrand distance and can only elongate by unwinding. Interstrand distance is directly correlated with the slide base-pair parameter and its different behavior in dsDNA and dsRNA traced down to changes in the sugar pucker angle of these NAs.